To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile approximately 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.

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To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and fulllength transgenic models of HD took longer to appear, 15-and 22-month CHL2 that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials.

The development of high-performance shielding materials against electromagnetic pollution requires mobile charge carriers and magnetic dipoles. Herein, we meet the challenge by building a three-dimensional (3D) nanostructure consisting of chemically modified graphene/Fe3O4(GF) incorporated polyaniline. Intercalated GF was synthesized by the in situ generation of Fe3O4 nanoparticles in a graphene oxide suspension followed by hydrazine reduction, and further in situ polymerization with aniline to form a polyaniline composite. Spectroscopic analysis demonstrates that the presence of GF hybrid structures facilitates strong polarization due to the formation of a solid-state charge-transfer complex between graphene and polyaniline. This provides proper impedance matching and higher dipole interaction, which leads to the high microwave absorption properties. The higher dielectric loss (ε'' = 30) and magnetic loss (μ'' = 0.2) contribute to the microwave absorption value of 26 dB (>99.7% attenuation), which was found to depend on the concentration of GF in the polyaniline matrix. Moreover, the interactions between Fe3O4, graphene and polyaniline are responsible for superior material characteristics, such as excellent environmental (chemical and thermal) degradation stability and good electric conductivity (as high as 260 S m(-1)).